Psychotic Disorders

Question 1

Definition of psychosis

Answer 1

A severe mental disorder in which thought and emotions are so impaired that contact is lost with reality

Question 2

What are hallucinations, what are the most common forms of hallucination. What is thought echo?

Answer 2

Hallucinations= A perception which occurs in the absence of an external sensory stimulus:

• Most commonly auditory
• 2^nd Person: Addressing patient directly
• 3^rd Person: discussing patient in the first person
• May be a running commentary or a ‘thought echo’ whereby they repeat patient’s thoughts.
• May be command hallucunations
• Rarely visual, somatic or olfactory

Question 3

What is a delusion. When can it be diagnosed

Answer 3

An impression maintained despite being contradicted by reality or rational argument that is fixed, unshakable and which cannot be explained by a patient’s cultural, religious or educational background.

• A symbolic misinterpretation that is accompanied by a strong sense of conviction (belief is entrenched)
• Lack of rational grounds and fixity
• Occur in roughly 50% of people with schizophrenia
• Often accompany paranoia- exaggerated, self-referential, sense of threat to self
• May simply be in a delusional mood- A strange, uncanny mood in which environment appears to be changed in a threatening way that is not understood. These experiences may then solidify into beliefs

Question 4

What are the components of insight in schizophrenia

Answer 4

• Acknowledgement of mental illness
• Appropriate attribution of symptoms
• Acceptance of need for treatment
• Awareness of the consequences of the disorder

Question 5

ICD10 classification of schizophrenia

Answer 5

‘A Fundamental distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness is usually maintained.’

• The course can be continuous or episodic, or can be one or more episodes with complete or incomplete remission
• However, a person should have had symptoms for at least one month
• It must occur in the abscence of extensive depressive or manic symptoms, overt brain disease, drug intoxication or withdrawal
• So hard to diagnose, especially after one consultation

Question 6

DSM-5 classification of schizophrenia

Answer 6

Requires the presence of delusions, hallucinations, disorganised speech and behaviour PLUS social or occupational dysfunction

Question 7

What are the classifications (types) of schizophrenia

Answer 7

• Paranoid schizophrenia: dominated by relatively stable paranoid delusions, usually accompanied by auditory hallucinations
• Catatonic schizophrenia: prominent psychomotor disturbance – hyperkinetic or stupor)
• Residual schizophrenia: Chronic - “negative” symptoms dominate with poor self-care and social performance)
• Hebephrenic schizophrenia: onset aged 15-25 years with disorganised and chaotic mood, behaviour and speech. Affect is shallow and inappropriate. Delusions are not prominent
• Simple schizophrenia: Only negative features are present, with no psychotic features.
• Persistent delusional disorder: either a s_ingle or a set of related delusions in the absence of auditory hallucinations_, delusions of control, blunting of affect, and brain disease
• Acute and transient psychotic disorders: acute onset of psychotic symptoms - delusions hallucinations disruption of ordinary behaviour - within two weeks or less. Complete recovery usually occurs within days (up to a few months). Often associated with acute stres

Question 8

What are Schneider’s First-rank symptoms

Answer 8

• Auditory hallucinations - Third person, running commentary, thoughts spoken aloud (‘thought echo’)
• Passivity experiences - delusions of control e.g. made feelings and impulses
• Thought interference- the patient believes that their thoughts are cotrolled by someone/something else. These delusions share the same subjective sense that something abnormal is happening to their thoughts
  
  • Thought withdrawal - thoughts being taken out of head
  • Thought insertion - thoughts ascribed to other people who are intruding into the patient’s mind
  • Thought broadcasting- thoughts are withdrawn, then publicly disseminated
• Delusional perception - linking normal perception to a bizarre conclusion e.g. see red car = I knew I had 2 souls

These are not diagnostic

Question 9

What are the negative symptoms of schizophrenia

Answer 9

• Social withdraw
• Reduction in speech production
• Apathy
• Anhedonia (inability to experience pleasure)
• Defects in attention control

Question 10

What are the cognitive symptoms of schizophrenia

Answer 10

• Memory-immediate and delayed recall, verbal and spatial memory
• Attention- slowed cognitive speed
• Executive function– poor sequencing, organisation, switching set

Question 11

What are the three phases described in schizophrenia (clinical course)

Answer 11

1. At risk mental state (ARMS)- ‘prodrome’
2. Acute phase
3. Chronic phase

Question 12

Describe the At risk mental state (ARMS)- ‘prodromal’ stage of schizophrenia

Answer 12

• About 20-30% of people with ARMS go on to develop psychosis (half of whom meet the criteria for schizophrenia classification)
• May include a period of very mild or brief cognitive symptoms, a change in mindset such as social withdrawal or loss of interest in activities- may deny psychotic symptoms.

Question 13

Describe the acute phase of schizophrenia

Answer 13

• Development of striking and florid psychotic features- formal thought disorder is common- thoughts become muddled, making speech disorganised. May develop pressure of speech or thought block.
• Behaviour may be withdrawn, overactive or bizarre
• Develop delusions or hallucinations
• May have a number of psychotic episodes over the course of years with full or partial recovery between episodes

Question 14

Describe the chronic phase of schizophrenia

Answer 14

• Over time patients may develop chronic ‘negative symptoms’ including apathy, blunted affect, anhedonia, social withdrawal and poverty of speech or thought.
• may manifest as- lack of attention to personal hygiene and care, limited repertoire of social activities or social isolation

Question 15

What is the point and lifetime prevalence of schizophrenia? when is the peak onset? Is it more prevalent in males or females?

Answer 15

• Prevalence ~0.7%
• Lifetime prevalence ~1.5%
• Peak onset in late adolescence and early adulthood (but can occur any time between childhood and late life)
• More prevalent in men than women 3:2à Onset later for women (25-35) than for men (18 and 25)
• Higher incidence in people from some ethnic minority communities (AESOP study: x9.0 Afrocaribbeans, x5.8 in black Africans, x1.4 in South Asians)

Question 16

Why is the incidenece of schizophrenia increased in some ethnic groups?

Answer 16

1. Selective migration
2. Perinatal infection- compatible with higher rates I second generation, however, does not explain high rates in north African migrants in Europe
3. Substance misuse: however cannabis use is unlikely to be higher
4. Discrimination and social issues: likely to be a driving factor- more efforts are needed to explore this

Question 17

What is the most importanmt risk factor for the development of schizophrenia?

Answer 17

• Genetic factors- most important factor (50% twin concordance rate), additionally lifetime risk 10x higher in first degree relatives of a person with psychosis and 40x if both parents are affectedà multiple susceptibility genes may interact (neurodevelopment, synaptic pruning)
• 10% lifetime risk for first-degree relatives of people with schizophrenia

Question 18

Aside from genetics, what are some other risk factors for schizophrenia?

Answer 18

• Perinatal trauma – pre-eclampsia, emergency c-section, IUGR, maternal malnutrition and stress
• Higher rates of psychosis occur amongst people who are born in the winter months- perhaps due to increased rates of perinatal infection
• Paternal age (Malaspina et al. 2001)- likely due to risk of genetic mutation
• Substance use disorders- Some drugs (cannabis, amphetamines, cocaine NPS) produce psychotic symptoms which wear off. May also trigger a relapse in someone with a history of psychotic illness.
• Cannabis-
• Neither sufficient nor necessary. But may be responsible for 12% of psychosis in Europe and 30% in UK (Di Forti et al. 2019)
• Childhood adversity and social disadvantage

Question 19

What psychotic symptoms are cannabis use associated with

Answer 19

• Associated with increased positive symptoms, and violence and aggression
• Associated with poorer response to antipsychotics, poorer adherence to medication
• Psychosis is likely triggered by cannabis use rather than the other way round
• The risk is heightened by skunk, a form of cannabis with higher concentrations of psychoactive tetrahydrocannabidiol (THC)

Question 20

What is the neurodevelopmental theory of schizophrenia

Answer 20

• Brain changes in some people with schizophrenia include enlarged ventricles, reduced cortical, amygdala and hippocampal volume and disorganisation of white matter tracts in the frontal/temporal region.
• Children who will eventually develop schizophrenia may develop neurological signs, lower IQ and deficits in learning and executive and social function.

Question 21

What is the dopamine theory of schizophrenia

What dopamine pathways are associated with positive symptoms and negative symptoms

Answer 21

• Excessive dopamine in the mesolimbic tracts (normally involved in reinforcement and reward) is thought to mediate the positive symptoms of psychosis (delusions and hallucinations).
• Dopamine deficiency in the mesocortical circuit and ventromedial prefrontal cortex is key in the aetiology of negative and cognitive symptoms of schizophrenia.
• The orbitofrontal cortex and its connections to the amygdala appears linked with aggressive and impulsive symptoms

Question 22

What are the four dopamine pathways

Answer 22

• Mesolimibic pathway (positive symptoms)
• Mesocortical (negative symptoms)
• Nigrostriatal (Extrapyramidal side effects)
• Tuberoinfundibular (hyperprolactinaemia)

Question 23

What is the importance of the mesolimbic pathway in schizophrenia

Answer 23

• Connects dopaminergic cell bodies in the ventral tegmental area (VTA) of the midbrain to the ventral striatum of the basal ganglia (limbic region) in the forebrain
  
  • Excess dopamine mediates +ve symptoms of psychosis

Question 24

What is the importance of the mesocortical pathway in schizophrenia

Answer 24

• Connects dopaminergic cell bodies in the VTA to the prefrontal cortex. It is essential for normal cognitive function and is thought to be involved in cognitive control, motivation, and emotional response
  
  • Deficient dopamine mediates –ve symptoms of psychosis

Question 25

What is the importance of the nigrostriatal pathway in schizophrenia

Answer 25

• Projects from the dopaminergic cell bodies in the substantia nigra (midbrain) to axons terminating in the striatum/basal ganglia.
• This pathway is part of the extrapyramidal nervous system and controls motor movements.
• Deficiency of dopamine in this pathway causes extrapyramidal side effects (EPSEs).
• Hyperactivity in this pathway underlies various hyperkinetic movement disorders such as chorea, dyskinesia and tics

Question 26

What is the importance of the tuiberoinfundibular pathway in schizophrenia

Answer 26

• This pathway projects from dopaminergic neurons in the hypothalamus to the anterior pituitary gland. Normally these dopaminergic neurons are active and work to inhibit the release of prolactin.
• During the postpartum period these neurons become less active and prolactin levels rise, causing lactation for breastfeeding

Question 27

What are some differentials for a first episode of psychosis

Answer 27

After first episode of pshycosis we should avoid using specific labels such as schizophrenia or schizoaffective disorder- should be ‘psychosis’ or ‘first-episode psychosis’ until recurrence

• Affective psychosis –> Affect will allow differentiation- in psychosis your mood is often incongruent with content of their belief. Additionally, these patients are less likely to have 1st rank symptoms. They are likely to have increased volume of speech, flight of speech etc. whereas thought disorder in psychosis is more likely to be alogia.
• Schizoaffective disorder: is diagnosed when there is a picture of schizophrenia, but with a mood disorder developing simultaneously. In contrast to a primary mood disorder such as BPAD, where psychotic symptoms emerge only as the mood becomes more extreme i.e BPAD with psychotic symptoms
• Schizotypal disorder: an enduring state which lasts at least several years or more. Eccentricity is central to the diagnosis (dressing, behaving or speaking oddly)
• Persistent delusional disorder: delusions with few (if any) hallucinations
• Acute and transient disorder: can resolve completely within a few months, linked to stress
• Drug-induced psychosis (drugs such as cannabis, khat and ketamine can acutely induce paranoia and thought disorder, rarely produce negative symptoms, symptoms resolve with drug cessation). Do a UDS
• Delirium (visual hallucinations, disorientated, foggy ‘clouding of consciousness’)
• Personality disorder (‘fleeting’ psychotic-like symptoms, insight preserved) should be considered if there is a lifelong pattern of interpersonal difficulties (schizoid PD lack of interest in social norms, paranoid PD suspicion and paranoia, borderline personality pattern gives brief psychotic or psychotic-like symptoms can occur in stress)

Question 28

What are some physical health conditions that can mimic psychosis

Answer 28

• Physical health conditions: metabolic disturbance, systemic infection, stroke, endocrine (hyperthyroidism, hypothyroidism), neurodegenerative diseases (Huntington’s disease, frontotemporal dementia, Lewy body), drug treatments (steroids, anti-Parkinson’s, withdrawal from BNZPs)

Question 29

What investigations are required for a rist epoisode psychosis

Answer 29

• History and mental state examination + collateral
• Physical examination (neurological system, cardiovascular system incl. weight, blood pressure) baseline ECG before starting antipsychotics
• Urine drug screen
• Blood tests (FBC, electrolytes, HbA1c, lipids, endocrine tests)
• EEG when investigating TLE or post-ictal symptoms

Use MRI/ CT to exclude organic causes if indications from history/physical examination (MRI may influence clinical management in approximately 5% of people with psychosis)

Question 30

Management: What social interventions can be performed

Answer 30

• Early Intervention in Psychosis (EIP) Service
  
  • Psychosis is toxic: the longer a patient is psychotic, the more it will affect their cognitive abilities, insight and social situationà The sooner effective treatment can be started the better the prognosis
  • The service aims to engage patients with very early symptoms, from adulthood till ~35 years
  • Patients are offered antipsychotics and psychosocial interventions with the aim of keeping the duration of untreated psychosis (DUP) under 3 months
  • The service can be used in children >14 years old
  • CAMHS can manage psychosis in children up to 17 years old
• If urgent resolution is required, can utilise the crisis resolution team and home treatment team
• Other services include Care-coordination: monitoring mental and physical health, medication, drug use, identifying and resolving social problems (supported accommodation) and Assertive outreach: maintaining contact with patients who may not want contact with services
• Psychoeducation is vital to reduce relapse
• Needs to address:
  
  • Education, training and employment
  • Skills (e.g. budgeting, cooking)
  • Housing (e.g. supported accommodation, independent flats)
  • Accessing social activities
  • Developing personal skills (e.g. creative writing)
  • Support for carers

Question 31

What psychological interventions can be used

Answer 31

• CBT: 16 or more one-to-one sessions over six months, decreases positive symptoms 29% compared to TAU
• Family interventions: 10 group sessions over 6-12 months > The patient is encouraged to talk to their family about what helps and is unhelpful. Aims to improve relationships by encouraging people to listen to each other and negotiate potential solutions
• Art therapy- particularly used for alleviation of negative symptoms

Question 32

What biological interventions can be used

Answer 32

• Antipsychotics
• Help with smoking cessation (nicotine replacement etc.) or substance misuse disorder
• Physical health e.g interventions for metabolic complications of antipsychotics

Question 33

What are typical antipsychotic drugs, give some examples

Answer 33

• Also known as First Generation Antipsychotics (FGAs)
• Examples – Chlorpromazine, Haloperidol, Zuclopenthixol (Clopixol), Flupentixol (Depixol)

Question 34

What are atypical antipsychotics, why are they preferred and what is the MoA

Answer 34

• Also known as Second Generation Antipsychotics (SGAs)
• Examples – Clozapine, Olanzapine, Quetiapine, Risperidone, Paliperidone, Aripiprazole, Lurasidone, Cariprazine
• Generally now preferred due to reduced side effect profile- lower risk of extrapyramidal side effects
• Atypicals all act as antagonists at the 5HT-2A serotonin receptor- this has downstream effects to increase dopamine in the nigrostriatal pathway (decreased extrapyramidal side effects)
• Aripiprazole, cariprazine and luradisone are all partial agonists

Question 35

How quickly can antipsychotics be expected to work?

Answer 35

The sedative effects of antipsychotics should occur within minutes to hours, and should begin exerting a clear antipsychotic effect after 1-2 weeks > maximum effect should be seen after 6 weeks

Question 36

What are long-acting injectable antipsychotics, what are their advantages

Answer 36

Long-acting injectable antipsychotics (LAIs) are also known as depots- given via a long-acting intramuscular injection rather than as an oral tablet. This is beneficial for patients with poor oral compliance (lack of insight.) However, not all oral tablets are available as depots. Adherence to treatment is around 50% in the first years BUT 10 days after discharge, 25% are partially non-adherent. Adherence to depots is around 75%.

Question 37

Give some examples of depots

Answer 37

• Zuclopenthixol (Clopixol) – Given every 1-4 weeks
• Flupentixol (Depixol) Given every 1-4 weeks
• Haloperidol (Haldol) – Given every 4 weeks
• Olanzapine (Zyprexa) – Given every 2-4 weeks
• Paliperidone (risperidone metabolite) – Available as 4 weekly, 3 monthly (Trevicta) and soon to be 6 monthly (Hafyera) à need to cross titrate from risperidone
• Aripiprazole (Abilify) – Given every 4 weeks

Question 38

What percentage of dopamine receptors need to be blocked to observe an effect of antipsychotics

Answer 38

Generally we need to achieve 60-80% block of dopamine receptors in order for clinical benefit to be seen

Start at low doses to minimise side effects, especially in those who are antipsychotic naïve as they are at higher risk of experiencing extrapyramidal side effects, this should be even lower in elderly people

Question 39

What are the five main side effects of antipsychotic medication

Answer 39

1. Hyperprolactinaemia 2. QTc Prolongation 3. Neuroleptic Malignant Syndrome 4. Extrapyramidal Side Effects 5. Metabolic syndrome

Question 40

What is hyperprolactinaemia and how is it managed

Answer 40

• Prolactin produced by the anterior pituitary gland
• Release stimulated by thyrotropin-releasing hormone (TRH) from hypothalamus
• Physiological role is to stimulate lactation postpartum
• Release is supressed by dopamine as part of the tuberoinfundibular pathway
• Defined as elevated serum prolactin à >530 women mIU/L, >424 men mIU/L
• Clinically significant if >1,000 mIU/L, otherwise can broadly be considered physiological
• Can also occur rarely after use of antidepressants
• Incidence is 34-42% in men and 59-75% in women on antipychotics
• Often asymptomatic • Women – Reduced libido, amenorrhoea, galactorrhoea, osteoporosis breast cancer • Men – Reduced libido, erectile dysfunction, gynaecomastia, galactorrhoea
• Management – Switch to a prolactin sparing agent, add in aripiprazole (partial dopamine agonist), dopamine agonists are generally avoided (e.g. carbergoline, bromocriptine)
• Prolactinoma will produce prolactin >3180 mIU/L

Question 41

What are the risks of QTc prolongation, how can it be managed

Answer 41

• QTc prolongation is a risk factor for developing cardiac arrhythmias
  
  • Specifically polymorphic ventricular tachycardia (Torsade de Pointes)
  • Risk increases significantly in QTc intervals >500ms
• Consider other risk factors • Hypokalaemia • Hypomagnesaemia • Hypocalcaemia • Liver disease, renal disease, hypothyroidism • Other medication – Citalopram, venlafaxine, clarithromycin, fluconazole
• Management- switch to a more QTc sparing agent- Aripiprazole (less side effects in general), Zuclopenthixol

Question 42

What are the signs and symptoms of NMS. how is it investigated and how can it be managed

Answer 42

• An acute potentially life-threatening complication of antipsychotic treatment
  
  • A disorder of thermoregulation and neuromotor control
  • Risk factors – High dose typicals, rapid dose changes, male gender, younger age
  • Occurs in <1% of patients
• Signs and symptoms:
  
  • Muscle rigidity
  • Hyperthermia
  • Hyporeflexia
  • Diaphoresis (sweating)
  • Autonomic dysregulation (e.g. tachycardia, hypotension)
  • Altered consciousness
• Investigations à Raised creatine kinase (CK) • Leucocytosis • Deranged liver function • Deranged renal function (secondary to Rhabdomyolysis from raised CK)
• STOP CAUSATIVE antipsychotic and transfer to ITU with supportive care and fluids. Give benzos and bromocriptine

Question 43

What are the four main extra-pyramidal side effect abnormalities

Answer 43

• Four main abnormalities are observed
  
  • Dystonia
  • Tardive dyskinesia
  • Akathisia
  • Parkinsonism
• These abnormalities are mediated by dopamine blocked within the nigrostriatal dopamine pathway

Question 44

Tardive dyskinesia symptoms and management

Answer 44

• An involuntary orofacial dyskinesia associated with long term antipsychotic use- seen as continuous mouth and tongue movement- ‘lip smacking’ and may also involve jaw clenching etc.
• May become permanent even if medication stopped > stop medication and consider tetrabenzine

Question 45

Dystonia symptoms and management

Answer 45

• Involuntary muscle spasm/ contractions. Develops acutely, within hours. Can affect any part of the body. RFs: antipsychotic naïve, young male, high dose drug tx.
• GIVE ANTICHOLINERGICS (procyclidine)

Question 46

Akathisia symptoms and management

Answer 46

• A sense of internal restlessness. The patient feels compelled to constantly move, rock, fidget or pace around. Very unpleasant! And associated with an increased risk of suicide. Occurs within days to weeks of starting tx.
• Management – Change medication, Diphenhydramine, Propranolol, low dose benzodiazepines

Question 47

Drug-induced parkinsonism symptoms and management

Answer 47

• Clinical Parkinson’s disease seen when 80-90% of dopamine neurons are lost in the subtantia nigra pars compact due to Lewy Body formation. Classic Parkinsonian symptom tetrad may be seen. Generally bilateral, whereas classical disease is asymmetrical.
• Can do a dopamine transporter scn (DAT scan). SWITCH MEDICATION and add in a regular antimuscarinic (Procyclidine)
  
  • Core features: Bradykinesia, rigidity, pill rolling tremor (4-6 Hz), postural instability
  • Additional features – Hypomimia, festinating gait with reduced arm swing

Question 48

How can atypical antipsychotics affect metabolic parameters

Answer 48

Can cause metabolic syndrome (average 20 year reduction in life expectancy amongst patients with psychosis)

Question 49

Monitoring required before commencing antipsychotic treatment

Answer 49

• Baseline Measurements before starting an antipsychotic:
  
  • Weight, Waist circumference, Pulse and BP
  • Fasting BM, HbA1c, lipid profile, prolactin
  • Assessment of any movement disorders
  • Assessment of nutritional status, diet and physical activity
  • ECG (if cardiovascular risk factors present or recommended by the chosen medication)

Question 50

Monitoring to be performed during antipsychotic treatment

Answer 50

• Emergence of movement disorders
• Waist circumference
• Adherence
• Overall physical health > Weight • Weekly for 6 weeks • At 12 weeks • At 1 years • Annually thereafter, Pulse and blood pressure • At 12 weeks • 1 year • Annually

Question 51

What is the indication for clozapine

Answer 51

• The best drug to treat treatment-resistant illness (unresponsive to two other drugs, one of which was atypical, when given at a therapeutic dose for at least 6 weeks)
• Has a bit of “magic” that other antipsychotics do not and is the gold-standard
• 1/3rd with treatment-resistant illness will respond very well to clozapine
• The only medication with evidence to treat negative symptoms- significantly decreases the suicide rate from schizophrenia

Question 52

What are the side effects of clozapine, what should be monitored and when

Answer 52

• Structurally similar to other “pines” > Olanzapine, Mirtazapine, Quetiapine > All block H1 receptors and cause sedation and increased appetite
• Causes sedation and increased appetite
  
  • Hypersalivation
  • Cardiomyopathy
  • Tachycardia
  • Hypotension
  • Myocarditis
  • Lowering of seizure threshold
  • Prothrombotic (more so than other antipsychotics) leading to risk of DVT/PE
  • Neutropenia/leucopenia/agranulocytosis (fatal in 0.03%)
  • Severe constipation
  • High risk of rebounding if stopped acutely
• Must be started at a low dose and titrated slowly due to the risk of cardiovascular instability > Must be re-titrated if stopped for more than 48 hours
• Patients require regular FBC monitoring due to the risk of neutropenia/leucopenia/agranulocytosis (approximately 1% of patients)
  
  • Initially weekly for 18 weeks, then fortnightly and monthly after 1 year of treatment

Question 53

What drugs can be used for rapid tranquilization in agitated patients

Answer 53

• They can be given PO or IM > IM administration is termed “rapid tranquilisation” and is often undertaken with the use of restraint
• Olanzapine and haloperidol are most commonly used
• Cautions- Pre-treatment ECG needed with haloperidol due to risk of QTc prolongation
• IM olanzapine not to be given within 1 hr of IM lorazepam due to risk of respiratory depression
• No more than 3 days of IM olanzapine to be given in a row due to risk of post-injection syndrome
• Should really only try antipsychotics after benzos and promethazine

Question 54

What is the recovery rate from schizophrenia. What factors predispose to poorer outcomes

Answer 54

• At 5 years: 25% completely recovered, 40% have periods or intervals of recovery lasting several years, 10% sustained deterioration with reduced social functioning and negative symptoms, remainder episodic (Harrow et al 2005)
• Prognosis worse if early onset
• Shorter ‘duration of untreated psychosis’ predicts better response to antipsychotic medication
• Better in resource-poor countries
• Reduced life expectancy – predominantly resulting from cardiovascular disease. 5-10% die by suicide (incidence increased by depressive symptoms, hopelessness, higher IQ, alcohol misuse, esp. in period following discharge.)